Tissue-specific overexpression or activation of 14-3-3 proteins have not been carried out, hence it is unclear whether the spectrum of morphological changes seen in CFC syndrome can be faithfully recapitulated if 14-3-3ζ is activated from its endogenous locus or replaced with a S230W equivalent allele in Xenopus. Nevertheless, our studies demonstrate that the Xenopus model can be used effectively to determine functional consequences of human genetic variants. Here, YWHAQ is linked to cardiofaciocutaneous syndrome.